Peptide having cancer selective translocation function and use thereof

ABSTRACT

The present invention relates a peptide having cancer selective translocation function, and the use thereof, and more particularly to a VEGF-binding protein transduction domain (VPTD) represented as SEQ ID NO: 1 or a heparin-binding protein transduction domain (HPTD) represented as SEQ ID NO: 2, which bind specifically to VEGF and heparin, which are overexpressed specifically in tumor cells or tumor tissues, and to a conjugate comprising a drug linked to the peptide. 
     The peptide and the peptide-drug conjugate bind specifically to VEGF and heparin in tumor cells or tumor tissue and accumulate in the tumor cells or tumor tissue, and thus can be used for the accurate diagnosis and treatment of cancer. Also, the non-specific distribution of the peptide or the conjugate in the body after administration is inhibited, and thus the side effects thereof can be minimized. Accordingly, the peptide or the conjugate is useful for the diagnosis and treatment of cancer.

TECHNICAL FIELD

The present invention relates to a peptide having cancer selectivetranslocation function, and the use thereof, and more particularly to apeptide having cancer selective translocation function, a conjugatecomprising a drug such as an anticancer agent linked to the peptidehaving cancer selective translocation function, and the use thereof.

The peptide having cancer selective translocation function of thepresent invention or a conjugate of the peptide and a drug canselectively penetrate tumor cells or tumor tissues, and thus can bewidely used for the diagnosis or treatment of various cancers.

BACKGROUND ART

For the treatment of tumors or the diagnosis and treatment ofinflammations, for example, osteoarthritis, and skin diseases, manystudies have been conducted on proteins or small materials, which arepresent specifically in disease foci. Thus, many kinds of such materialshave been identified while studies on treatment with such materials havealso been actively conducted. For example, it was shown thatprostate-specific antigen (PSA) is frequently present in prostatecancer, and matrix metalloprotease (MMP) is highly expressedspecifically in arthritis tissue or other tumor tissues compared to thatin normal tissue. Thus, such materials have been targeted in diseaseresearch and treatment. However, if materials that are used for thediagnosis and treatment of diseases do not act specifically against suchtargets only, problems of side effects and low image quality will becaused by non-specific distribution of the materials. For this reason,there has been a demand for the development of formulations that remainor act specifically in their targets.

Meanwhile, only some small materials can enter the cytoplasm or nucleusof live cells through the cell membrane at a very low ratio, whereaslarge molecules cannot enter cells. Because most materials prepared fortherapeutic, preventive or diagnostic purposes, each of which requiresan effective amount to be delivered into cells, are large molecules ormacromolecules, methods of delivering biologically active macromoleculesinto cells without damaging the cells both in vivo and ex vivo have beendemanded.

As a result of studies conducted to satisfy this demand, proteintransduction domains (PTDs) have been suggested, and among them, TATprotein, which is the transcription factor of human immunodeficiencyvirus-1 (HIV-1), has been most frequently studied. It was found that theTAT protein is more effective in passing through the cell membrane whenit is composed of amino acids 47 to 57 (YGRKKRRQRRR), on whichpositively charged amino acids are concentrated, compared to when it isin a full-length form consisting of 86 amino acids (Fawell, S. et al.,Proc. Natl. Acad. Sci. USA, 91:664, 1994). Other examples verifying theeffects of PTDs include a peptide having a sequence of amino acids 267to 300 of the VP22 protein of Herpes Simplex Virus type 1 (HSV-1)(Elliott, G. et al., Cell, 88:223, 1997), a peptide having a sequence ofamino acids 84 to 92 of the UL-56 protein of HSV-2 (GeneBankcode:D1047[gi:221784]), and a peptide having a sequence of amino acids339 to 355 of the Antennapedia (ANTP) protein of Drosophila sp(Schwarze, S. R. et al., Trends. Pharmacol. Sci., 21:45, 2000). Inaddition, artificial peptides consisting of positively charged aminoacids also showed the effect of delivering drugs (Laus, R. et al.,Nature. Biotechnol., 18:1269, 2000).

Recently, the present inventors reported the preparation of alow-molecular-weight protamine (LMWP) and the cell-penetrating activitythereof, in which the low-molecular-weight protamine (LMWP) has apeptide sequence similar to TAT, serves as a protein transduction domainand contains a large amount of cationic amino acids such as arginine.Particularly, the LMWP peptide is a naturally occurring cationic peptidefrom protamine and is advantageous in that it presents no toxicityconcerns and can be produced in large amounts (Park, Y. J. et al., J.Gene. Med., 700, 2003). Meanwhile, the present inventors have found thatthe LMWP peptide selectively binds to vascular endothelial growth factor(VEGF) and heparin, which are distributed specifically in tumor tissue,and have expected that the peptide would have the effect of selectivelyinhibiting tumors. Meanwhile, this LMWP peptide will hereinafter bereferred to as “VEGF-binding protein transduction domain (VPTD) orpeptide”.

The present inventors have found that a VEGF-binding proteintransduction domain (VPTD) peptide represented as SEQ ID NO: 1 or aheparin-binding protein transduction domain (HPTD) peptide representedas SEQ ID NO: 2 binds specifically to vascular endothelial growth factor(VEGF) and heparin in tumor cells or tumor tissues and also accumulatesselectively in tumor cells or tumor tissues to inhibit the growth of thetumor cells, thereby completing the present invention.

DISCLOSURE OF INVENTION

It is an object of the present invention to provide a peptide which canminimize problems associated with side effects or low image quality,which can occur due to the non-specific distribution of conventionaltumor diagnostic or therapeutic agents, in which the peptide can delivertumor diagnostic agents or disease therapeutic agents selectively totarget cells only.

Accordingly, a main object of the present invention is to reconstitutethe oxidation/reduction balance in mutant strains, which lack each of472 genes involved in breathing, electron transfer andoxidation/reduction reactions, at the genome-wide level by anaerobicfermentation, and based on the reconstitution, select genes capable ofcontrolling the carbon metabolic flow and provide a mutant microorganismin which lactic acid, succinic acid or ethanol is produced in largeamounts but the production of other organic acids is significantlyreduced, and a method for producing the mutant microorganism. Stillanother object of the present invention is to use the peptide for thediagnosis or treatment of cancer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the results of measuring the tumor cell-penetratingabilities of a VEGF-binding protein transduction domain (VPTD) peptiderepresented as SEQ ID NO: 1 (VSRRRRRRGGRRRR) and a heparin-bindingprotein transduction domain (HPTD) represented as SEQ ID NO: 2.Specifically, FIG. 1 a is a graphic diagram showing the results of flowcytometry, and FIG. 1 b is a set of confocal scanning microscope imagesshowing the observation of the results shown in FIG. 1 a.

FIG. 2 shows the results of examining the accuracy of synthesis of theinventive VPTD peptide represented as SEQ ID NO: 1 or the inventive HPTDpeptide represented as SEQ ID NO: 2 and measuring the binding affinitybetween the peptides and their targets, VEGF and heparin.

FIG. 3 shows the results of examining the tumor inhibitory effects ofthe inventive VPTD peptide represented as SEQ ID NO: 1, an anticanceragent (Dox; doxrubicin), and a conjugate of the VPTD peptide of SEQ IDNO: 1 and the anticancer agent (Dox).

BEST MODE FOR CARRYING OUT THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention pertains. Generally, the nomenclatureused herein and the experiment methods, which will be described below,are those well known and commonly employed in the art.

The definition of major terms used in the present invention is asfollows.

As used herein, the term “protein transduction domain (PTD)” refers to acell-penetrating peptide capable of delivering drugs or drug-containingparticles into the cytoplasm or nucleus of cells. Specifically, the termrefers to a peptide that can form a covalent bond with oligonucleotides,peptides, proteins, oligosaccharides, polysaccharides or nanoparticlesto introduce these materials into cells without needing to use aseparate receptor, carrier or energy. The inventive VEGF-binding proteintransduction domain peptide represented as SEQ ID NO: 1 and theinventive heparin-binding protein transduction domain peptiderepresented as SEQ ID NO: 2 are also included in the scope of the PTD.

As used herein, the term “tumor cell” or “tumor tissue” refers to an invivo or ex vivo cell or tissue into which a drug or a drug-containingparticle are delivered by a tumor-penetrating peptide. In other words,as used herein, the term “tumor tissue” is meant to include in vivocells, that is, cells that constitute the organ or tissue of livinganimals or humans, or microorganisms that are found in living animals orhumans.

In one aspect, the present invention provides peptide having cancerselective translocation function comprising VPTD (VEGF-binding proteintransduction domain peptide) peptide represented as SEQ ID NO: 1 or HPTD(heparin-binding protein transduction domain) peptide represented as SEQID NO: 2, and a composition for enhancing cancer selectivetranslocation, which comprises the peptide as an active ingredient.

The VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptiderepresented as SEQ ID NO: 2 is characterized in that it bindsspecifically to vascular endothelial growth factor (VEGF) and heparin intumor cells or tumor tissue (see FIG. 2). The expression level of VEGFor heparin in tumor cells or tumor tissue is higher than that in normaltissue, and thus the inventive peptide represented as SEQ ID NO: 1 or 2can bind specifically to tumor tissue or tumor cells. Also, the VPTDpeptide represented as SEQ ID NO: 1 or the VPTD peptide represented asSEQ ID NO: 2, according to the present invention, has the ability topenetrate cells, and thus can bind specifically to VEGF or heparin, andthen enter cells without having to use endocytosis that is aconventional intracellular absorption process. Thus, it can accumulateselectively in tumor cells or tumor tissue.

The VPTD peptide represented as SEQ ID NO: 1 or the VPTD peptiderepresented as SEQ ID NO: 2 may be composed of D-type or L-type aminoacids depending on in vivo stability and may contain one or more aminoacids selected from the group consisting of arginine, lysine andhistidine in an amount of 70-80%.

Examples of protein transduction domains (PTDs) having theabove-described characteristic include, in addition to the proteintransduction domains VPTD (SEQ ID NO: 1; VSRRRRRRGGRRRR) and HPTD (SEQID NO: 2; CSSRKKNPNCRRH) found by the present inventors, cationicprotein transduction domains having an arginine, lysine or histidinecontent of 70-80% or more, such as penetratin (SEQ ID NO: 3;RQIKIWFQNRRMKWKK), polyarginine (SEQ ID NO: 4; RRRRRRR), polylysine (SEQID NO: 5; KKKKKKKKKK), a protamine fragment, and Antennapedia (ANTP), aswell as defensin-derived HBD (SEQ ID NO: 6:GKCSTRGRKCCRRKK) and TAT (SEQID NO: 7: YGRKKRRQRRR). Thus, the PTDs of SEQ ID NO: 3 to SEQ ID NO: 7may also be used as a substitute for the peptide of SEQ ID NO: 1 or 2.

In another aspect, the present invention provides a method of using theVPTD peptide of SEQ ID NO: 1 or the HPTD peptide of SEQ ID NO: 2 todiagnose or treat cancer.

The VPTD peptide of SEQ ID NO: 1 or the HPTD peptide of SEQ ID NO: 2binds specifically to vascular endothelial growth factor (VEGF) andheparin in tumor cells or tumor tissue and accumulates in the tumorcells or tumor tissue, and thus the peptide can be used for thediagnosis or treatment of cancer.

In still another aspect, the present invention provides contrast agentfor cancer diagnosis having cancer selective translocation function,which comprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptiderepresented as SEQ ID NO: 2 to which a fluorescent substance is bound.

Because the VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptiderepresented as SEQ ID NO: 2 accumulates selectively in tumor cells ortumor tissues, a conjugate comprising a fluorescent substance bound tothe peptide may be used as a contrast agent for cancer diagnosis (seeExample 3 and FIG. 1).

The fluorescent substance that is used in the present invention may beselected from the group consisting of fluorescein isothiocyanate (FITC),radioisotopes, quantum dots, MRI contrast agents, fluorescein,tetramethylrhodamine, BODIPY, and Alexa, but is not limited thereto.

In yet another aspect, the present invention provides a composition fortreating cancer having cancer selective translocation function, whichcomprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptiderepresented as SEQ ID NO: 2.

Because the VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptiderepresented as SEQ ID NO: 2 according to the present invention shows theeffect of inhibiting the growth of tumor cells by its selective bindingto VEGF and heparin, which are highly expressed in tumor cells or tumortissue (see Examples 4 and FIGS. 2 and 3), the composition containingthe peptide may also be used as a composition for treating cancer.

In a further aspect, the present invention provide a peptide havingcancer selective translocation function-drug conjugate, which comprisesa drug chemically linked to the N-terminus or C-terminus of VPTD peptiderepresented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2.

The VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptiderepresented as SEQ ID NO: 2 and the drug may be linked to each other bya cysteine. Specifically, the peptide-drug conjugate is prepared bylinking a drug having a thiol group to the N-terminus or C-terminus ofthe peptide of SEQ ID NO: 1 or 2, which contains a cysteine. If theabove-described peptide analogue is used as a substitute for the peptideof SEQ ID NO: 1 or 2, the peptide-drug conjugate may also be prepared byattaching a cysteine to the terminus of the peptide, and then reactingthe peptide with a drug. Examples of the drug having a thiol groupinclude not only drugs that naturally contain a thiol group, but alsodrugs modified to have a thiol group.

In addition, the peptide-drug conjugate may also be prepared by linkingthe peptide with the drug by a crosslinking agent. Because theN-terminus of the protein transduction domain (PTD) peptide has a freeamino group, it is easy to form the peptide-drug conjugate by acrosslinking agent. Examples of the crosslinking agent that can be usedin the present invention include, but not limited to,1,4-bis-maleimidobutane (BMB), 1,11-bis-maleimidotetraethyleneglycol(BM[PEO]4), 1-ethyl-3-[3-dimethyl aminopropyl]carbodiimide hydrochloride(EDC),succinimidyl-4-[N-maleimidomethylcyclohexane-1-carboxy-[6-amidocaproate]](SMCC) and its sulfonate (sulfo-SMCC), succimidyl6-[3-(2-pyridyldithio)-ropionamido]hexanoate (SPDP) and its sulfonate(sulfo-SPDP), m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) andits sulfonate (sulfo-MBS), and succimidyl[4-(p-maleimidophenyl)butyrate] (SMPB) and its sulfonate (sulfo-SMPB). If the cell-penetratingpeptide and a drug or a drug-containing nanoparticle are linked to eachother by an S—S bond, the drug can be dissociated from thecell-penetrating peptide by reductase or the like in cells. If thismethod is used, drugs, proteins or other nanoparticles can be introducedinto cells in an easy and convenient manner without having to use arecombinant vector that is constructed in a time-consuming manner, andthus the desired therapeutic can be easily achieved.

Examples of the drug that is used in the present invention includeanticancer agents, anti-inflammatory agents, bone resorption inhibitors,anticancer proteins, anti-inflammatory proteins, immune-enhancingproteins, anticancer and anti-inflammatory siRNAs, oligonucleotides, andmagnetic nanoparticles containing them. As used herein, the term “siRNA”refers to RNA that silences the expression of the target RNA. The targetRNA is the mRNA transcribed from a gene that causes disease,particularly a tumor or inflammation. Examples of oncogenes include, butare not limited to, vascular endothelial growth factor (VEGF) gene.

The aforementioned protein that causes a tumor or inflammatory diseasemay be selected from the group consisting of vascular endothelial growthfactor (VEGF), B-cell leukemia/lymphoma 2 (BCL2), epidermal growthfactor receptor (EGFR), human epidermal growth factor receptor 2 (HER2),Janus kinase (JAN), and phosphatidylinositol-3-kinase/Akt kinase(PI3-K/AKT).

In a still further aspect, the present invention provides a drugdelivery system having cancer selective translocation function, whichcomprises a drug linked to the N-terminus or C-terminus of VPTD peptiderepresented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2.

In a yet further aspect, the present invention provides a compositionfor treating cancer comprising a peptide having cancer selectivetranslocation function-drug conjugate, which comprises a drug chemicallylinked to the N-terminus or C-terminus of VPTD peptide represented asSEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2.

The composition for treating cancer according to the present inventioncan be administered with a pharmaceutically acceptable carrier. Forexample, for oral administration, the composition of the presentinvention can comprise binders, lubricants, disintegrants, excipients,emulsifiers, dispersions, stabilizers, suspending agents, pigments,perfumes, etc., for injection administration, the composition cancomprises buffers, preservatives, analgesics, emulsifiers, isotonicagents, stabilizers, etc., and for local administration, the compositioncan comprises bases, excipients, lubricants, preservatives, etc.

The inventive composition for treating cancer can be formulated with apharmaceutically acceptable carrier as described above in variousmanners. For example, for oral administration, the composition of thepresent invention can be formulated in the form of tablet, troche,capsule, elixir, suspension, syrup, wafer, etc., and for injectionadministration, the composition can be formulated as a unit dosageampoule or a multiple dosage form.

The inventive composition for treating cancer can be administered in aneffective amount for the therapeutic or prevention purpose. The dose ofthe composition of the present invention may vary depending on variousfactors, such as disease type and severity, age, sex, body weight,sensitivity to drugs, type of current therapy, mode of administration,target cell, etc., and may be easily determined by those of ordinaryskill in the art. The composition of the present invention may also beadministered in combination with conventional therapeutic or preventiveagents for cancer, sequentially or simultaneously with the conventionaltherapeutic agents, and in single dose or multiple doses. Preferably,with all of the factors taken into account, it is imperative that theminimum dose required to achieve the maximum effect without side effectsbe administered, which can be easily determined by those of ordinaryskill in the art. As used herein, the term “administration” meansintroducing a desired material into a patient by any suitable method.The pharmaceutical composition of the present invention may beadministered through any general route, as long as it can reach adesired tissue. The composition of the present invention can beadministered intraperitoneally, intravenously, intramuscularly,subcutaneously, transdermally, orally, topically, intranasally,intrapulmonarily or intrarectally, but is not limited thereto. Inaddition, the pharmaceutical composition of the present invention mayalso be administered by any device that can deliver the activeingredient into target cells.

Particularly, although the following examples illustrated only theanticancer protein Gelonin as a drug, it will be obvious to thoseskilled in the art that the use of other anticancer proteins, anantisense oligonucleotide against an oncogene, an siRNA, or particlescontaining them, can also show tumor therapeutic effects that are equalor similar to those of the use of Gelonin, and that the use of ananti-inflammatory agent or an anti-inflammatory protein as a drug canalso show anti-inflammatory effects.

EXAMPLES

Hereinafter, the present invention will be described in further detailwith reference to examples. It will be obvious to a person havingordinary skill in the art that these examples are illustrative purposesonly and are not to be construed to limit the scope of the presentinvention.

Example 1 Preparation of Target-Selective Cell/Tissue-PenetratingPeptide

Peptides were prepared by the F-moc chemistry method using an automaticpeptide synthesizer, and then the peptide moieties were cut by resin,washed, freeze-dried, followed by purification by liquid chromatography,thereby preparing a VPTD peptide represented as SEQ ID NO: 1(VSRRRRRRGGRRRR) and an HPTD peptide represented as SEQ ID NO: 2(CSSRKKNPNCRRH). The molecular weights of the purified peptides wereanalyzed by MALDI.

Example 2 Preparation of Tumor-Targeting and Tumor-PenetratingPeptide-Drug Conjugates

The VPTD peptide of SEQ ID NO: 1 and the HPTD peptide of SEQ ID NO: 2,prepared in Example 1, contained the free-sulfhydryl group of a cysteineresidue, and thus chemical linkage between the peptide and theanticancer protein RNase or doxorubicin was induced using thefree-sulfhydryl group as a chemical crosslinking agent. The surfaces ofRNase and doxorubicin (Dox) were modified to have a thiol group attachedto the carboxyl group on the surfaces. 10 molecules of peptide-SH wereadded to 1 molecule of particle surface-SH and reacted at 4° C. for 12hours, and then unreacted molecules were removed by ultrafiltration,followed by freeze drying, thereby obtaining a conjugate of the VPTDpeptide of SEQ ID NO: 1 and RNase, a conjugate of the VPTD peptide ofSEQ ID NO: 1 and Dox, a conjugate of the HPTD peptide of SEQ ID NO: 2and RNase, and a conjugate of the HPTD peptide of SEQ ID NO: 2 and Dox.

Example 3 Tumor Cell Penetration Abilities of Tumor-Targeting andCell-Penetrating Peptides

In order to test the tumor cell-targeting and tumor cell-penetratingabilities of the VPTD peptide of SEQ ID NO: 1 and the HPTD peptide ofSEQ ID NO: 1, prepared in Example 1, the termini of the preparedpeptides were labeled with a fluorescent dye, and then each of thepeptides was inoculated into a tumor cell line (MDA-MB-231, ATCC) atvarious concentrations.

60 minutes after the inoculation, the fluorescence of the cells wasmeasured by FACS, and the results of the measurement are shown inFIG. 1. As can be seen in FIG. 1(A), the fluorescence of the tumor cellsincreased in a manner dependent on the concentration of the peptide.FIG. 1(B) shows the results of observing the fluorescence of the tumorcells by a confocal laser scanning microscope in order to examine thetumor cell penetration abilities of the VPTD peptide of SEQ ID NO: 1 andthe HPTD peptide of SEQ ID NO: 1. In FIG. 1(B), in order to demonstratethat the stained portion is the cells, the cell nuclei were stained withHoechst 33342 (5 μg/μl), and then the cells were fixed with 10% neutralformalin solution. As a result, as can be seen in FIG. 1(B), theabilities of the peptide to penetrate the tumor cell line increased in amanner dependent on the concentration of the peptide.

Example 4 Measurement of Tumor Inhibitory Effects of Tumor-Targeting andTarget-Penetrating Peptide-Anticancer Agent Conjugates

In order to test the effects of the VPTD peptide of SEQ ID NO: 1(VSRRRRRRGGRRRR) and the HPTD peptide of SEQ ID NO: 2 (CSSRKKNPNCRRH),prepared in Example 1, and the tumor-targeting and tumor-penetratingpeptide-drug conjugates prepared in Example 2, a tumor was induced inmice, and when the tumor grew to a predetermined size, each of thepeptides prepared in Example 1 and the tumor-targeting andtumor-penetrating peptide-drug conjugates prepared in Example 2 wasinjected into the mice. After injection, the volume of the tumor wasmeasured at intervals of 3-4 days for 30 days. On day 30, the mice weresacrificed, and the tumor was extracted and photographed.

As a result, as shown in FIG. 3, in the tumor-induced mice treated witha control, the tumor was not inhibited, whereas in the tumor-inducedmice treated with each of the VPTD peptide and the VPTD peptide-drug(Dox) conjugate, the progression of the tumor was significantlyinhibited. This is believed to be because the tumor-penetrating abilityof the VPTD peptide of the present invention was maximized in the tumortissue and the VPTD peptide did bind specifically to VEGF to inhibitvascular formation essential for the formation and progression oftumors. To demonstrate such results, the ability of the inventive VPTDpeptide of SEQ ID NO: 1 or the inventive HPTD peptide of SEQ ID NO: 2 tobind to VEGF and heparin was evaluated by slot-blot analysis. As aresult, it could be seen that the VPTD peptide and the HPTD peptide didall bind to VEGF and heparin, which are overexpressed in tumor cells ortumor tissue.

As described above, the tumor-targeting and tumor-penetrating peptide ofthe present invention and a conjugate of the peptide and a drug breakfrom conventional non-specific and non-selective transduction peptides,and can maximize the effects of diagnosis and drug therapies throughoptimal targeting, and the side effects thereof in the body can beminimized. Thus, the use of the tumor-selective and tumor-penetratingpeptide according to the present invention can present innovativedisease diagnostic and therapeutic technologies.

INDUSTRIAL APPLICABILITY

As described above, the peptide or peptide-drug conjugate of the presentinvention selectively penetrates tumor cells or tumor tissue only, andthus can be used for the diagnosis or treatment of cancer. Conventionaldrugs or materials that are used in the diagnosis or treatment of tumorscan cause unexpected side effects if they are distributednon-specifically in vivo, and in many cases, it is difficult to achieveaccurate diagnosis using the conventional drugs or materials. However,the use of the peptide of the present invention can solve such problems.

Although the present invention has been described in detail withreference to the specific features, it will be apparent to those skilledin the art that this description is only for a preferred embodiment anddoes not limit the scope of the present invention. Thus, the substantialscope of the present invention will be defined by the appended claimsand equivalents thereof.

1. A peptide having cancer selective translocation function comprisingVPTD (VEGF-binding protein transduction domain peptide) peptiderepresented as SEQ ID NO: 1 or HPTD (heparin-binding proteintransduction domain) peptide represented as SEQ ID NO:
 2. 2. The peptidehaving cancer selective translocation function of claim 1, wherein theVPTD peptide represented as SEQ ID NO: 1 or the HPTD peptide representedas SEQ ID NO: 2 binds specifically to vascular endothelial growth factor(VEGF) and heparin in tumor cells or tumor tissues.
 3. The peptidehaving cancer selective translocation function of claim 1, wherein theVPTD peptide represented as SEQ ID NO: 1 or the HPTD peptide representedas SEQ ID NO: 2 is composed of D-type or L-type amino acids and containsone or more amino acids selected from the group consisting of arginine,lysine and histidine in an amount of 70-80%.
 4. The peptide havingcancer selective translocation function of claim 1, wherein the VPTDpeptide represented as SEQ ID NO: 1 or the HPTD peptide represented asSEQ ID NO: 2 is composed of D-type or L-type amino acids and containsone or more amino acids selected from the group consisting of arginine,lysine and histidine in an amount of 70-80%.
 5. A contrast agent forcancer diagnosis having cancer selective translocation function, whichcomprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptiderepresented as SEQ ID NO: 2 to which a fluorescent substance is bound.6. The contrast agent for cancer diagnosis having cancer selectivetranslocation function of claim 5, wherein the fluorescent substance isselected from the group consisting of fluorescein isothiocyanate (FITC),radioisotopes, quantum dots, MRI contrast agents, fluorescein,tetramethylrhodamine, BODIPY, and Alexa.
 7. A composition for treatingcancer having cancer selective translocation function, which comprisesVPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented asSEQ ID NO:
 2. 8. A composition for enhancing cancer selectivetranslocation, which comprises VPTD peptide represented as SEQ ID NO: 1or HPTD peptide represented as SEQ ID NO: 2 as an active ingredient. 9.A peptide having cancer selective translocation function-drug conjugate,which comprises a drug chemically linked to the N-terminus or C-terminusof VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide representedas SEQ ID NO:
 2. 10. The peptide having cancer selective translocationfunction-drug conjugate of claim 9, wherein the VPTD peptide representedas SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2 and the drugare linked to each other by a cysteine.
 11. The peptide having cancerselective translocation function-drug conjugate of claim 9, wherein thechemical linkage of the drug to the peptide is performed by any onecrosslinking agent selected from the group consisting of1,4-bis-maleimidobutane (BMB), 1,11-bis-maleimidotetraethyleneglycol(BM[PEO]4), 1-ethyl-3-[3-dimethyl aminopropyl]carbodiimide hydrochloride(EDC),succinimidyl-4-[N-maleimidomethylcyclohexane-1-carboxy-[6-amidocaproate]](SMCC) and its sulfonate (sulfo-SMCC), succimidyl6-[3-(2-pyridyldithio)-ropionamido]hexanoate (SPDP) and its sulfonate(sulfo-SPDP), m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) andits sulfonate (sulfo-MBS), and succimidyl[4-(p-maleimidophenyl)butyrate] (SMPB) and its sulfonate (sulfo-SMPB).
 12. The peptide havingcancer selective translocation function-drug conjugate of claim 9,wherein the drug is selected from the group consisting of an antisenseoligonucleotide targeting RNA of a protein that causes a tumor orinflammatory disease, a siRNA targeting RNA of a protein that causes atumor or inflammatory disease, an anticancer agent, an anticancerprotein, an anti-inflammatory agent, an anti-inflammatory protein, animmune-enhancing protein, and a bone resorption inhibitor.
 13. Thepeptide having cancer selective translocation function-drug conjugate ofclaim 12, wherein the protein that causes a tumor or inflammatorydisease is selected from the group consisting of vascular endothelialgrowth factor (VEGF), B-cell leukemia/lymphoma 2 (BCL2), epidermalgrowth factor receptor (EGFR), human epidermal growth factor receptor 2(HER2), Janus kinase (JAN), and phosphatidylinositol-3-kinase/Akt kinase(PI3-K/AKT).
 14. A composition for treating cancer comprising a peptidehaving cancer selective translocation function-drug conjugate, whichcomprises a drug chemically linked to the N-terminus or C-terminus ofVPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented asSEQ ID NO:
 2. 15. The composition for treating cancer of claim 14,wherein the drug is selected from the group consisting of an anticanceragent, an anticancer protein, an antisense oligonucleotide targeting RNAof a protein that cause a tumor, and a siRNA targeting RNA of a proteinthat cause a tumor.
 16. A drug delivery system having cancer selectivetranslocation function, which comprises a drug linked to the N-terminusor C-terminus of VPTD peptide represented as SEQ ID NO: 1 or HPTDpeptide represented as SEQ ID NO:
 2. 17. The drug delivery system havingcancer selective translocation function of claim 16, wherein the drug isselected from the group consisting of an antisense oligonucleotidetargeting RNA of a protein that causes a tumor or inflammatory disease,a siRNA targeting RNA of a protein that causes a tumor or inflammatorydisease, an anticancer agent, an anticancer protein, ananti-inflammatory agent, an anti-inflammatory protein, animmune-enhancing protein, and a bone resorption inhibitor.